Skip to main content
SpringerLink
Log in

Effects of geometric isomerism in dinuclear antitumor platinum complexes on their interactions with N-acetyl-L-methionine

  • Minireview
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

An Erratum to this article was published on 26 October 2005

Abstract

In this study, the reactions of N-acetyl-L-methionine (AcMet) with [{trans-PtCl(NH3)2}2-μ-H2N(CH2)6NH2](NO3)2 (BBR3005: 1,1/t,t 1) and its cis analog [{cis-PtCl(NH3)2}2-μ-{H2N(CH2)6NH2}]Cl2 (1,1/c,c 2) were analyzed to determine the rate and reaction profile of chloride substitution by methionine sulfur. The reactions were studied in PBS buffer at 37°C by a combination of multinuclear (195Pt, {1H-15N} HSQC) magnetic resonance (NMR) spectroscopy and electrospray ionization time of flight mass spectrometry (ESITOFMS). The diamine linker of the 1,1/t,t trans complex was released as a result of the trans influence of the coordinated sulfur atom, producing trans-[PtCl(AcMet)(NH3)2]+ (III) and trans-[Pt(AcMet)2(NH3)2]2+ (IV). In contrast the cis geometry of the dinuclear compound maintained the diamine bridge intact and a number of novel dinuclear platinum compounds obtained by stepwise substitution of sulfur on both platinum centers were identified. These include (charges omitted for clarity): [{cis-PtCl(NH3)2}-μ-NH2(CH2)6NH2-{cis-Pt(AcMet)(NH3)2}] (V); [{cis-Pt(AcMet)(NH3)2}2-μ-NH2(CH2)6NH2] (VI); [{cis-PtCl(NH3)2}-μ-NH2(CH2)6NH2-{PtCl(AcMet)NH3] (VII); [{PtCl(AcMet)(NH3)}2-μ-NH2(CH2)6NH2] (VIII); [{trans-Pt(AcMet)2(NH3)}-μ-NH2(CH2)6NH2-{PtCl(AcMet)(NH3)] (IX) and the fully substituted [{trans-Pt(AcMet)2(NH3)}2-μ-{NH2(CH2)6NH2] (X). For both compounds the reactions with methionine were slower than those with glutathione (Inorg Chem 2003, 42:5498–5506). Further, the 1,1/c,c geometry resulted in slower reaction than the trans isomer, because of steric hindrance of the bridge, as observed previously in reactions with DNA and model nucleotides.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Scheme 1
Scheme 2
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Lempers ELM, Reedijk J (1991) Adv Inorg Chem 37:175

    Article  CAS  Google Scholar 

  2. Eastman A, Richon VM (1986) In: McBrien SCH, Slater TF (eds) Biochemical mechanisms of the platinum antitumor drugs. IRL Press Limited, Oxford, pp 91–119

  3. Reedijk J (1999) Chem Rev 99:2499–2510

    PubMed  CAS  Google Scholar 

  4. Ivanov AI, Christodoulou J, Parkinson JA, Barnham KJ, Tucker A, Woodrow J, Sadler PJ (1998) J Biol Chem 273:14721–14730

    PubMed  CAS  Google Scholar 

  5. Farrell N, Qu Y, Bierbach U, Valsecchi M, Menta E (1999) In: Lippert B (ed) 30 Years of cisplatin—chemistry and biochemistry of a leading anticancer drug. Wiley, New York, pp 479–498

  6. Farrell N, Appleton TG, Qu Y, Roberts JD, Soares Fontes AP, Skov KA, Wu P, Zou Y (1995) Biochemistry 34:15480–15486

    PubMed  CAS  Google Scholar 

  7. Kasparkova J, Novakova O, Vrana O, Farrell N, Brabec V (1999) Biochemistry 38:10997–11005

    PubMed  CAS  Google Scholar 

  8. Mellish KJ, Qu Y, Scarsdale JN, Farrell N (1997) Nucelic Acids Res 25:1265–1271

    CAS  Google Scholar 

  9. Oehlsen ME, Hegmans A, Qu Y, Farrell N (20050 Inorg Chem 44:3004–3006

    PubMed  CAS  Google Scholar 

  10. Oehlsen ME, Qu Y, Farrell N (2003) Inorg Chem 42:5498–5506

    PubMed  CAS  Google Scholar 

  11. Farrell N (1995) Comments in inorganic chemistry 16:373–389

    Google Scholar 

  12. Qu Y, Farrell N (1990) J Inorg Biochem 40:255–264

    CAS  Google Scholar 

  13. Kay LE, Keifer P, Saarinen T (1992) J Am Chem Soc 114:10663–10665

    CAS  Google Scholar 

  14. Appleton TG, Connor JW, Hall JR (1988) Inorg Chem 27:130–137

    CAS  Google Scholar 

  15. Murdoch SP, Ranford JD, Sadler PJ, Berners-Price SJ (1993) Inorg Chem 32:2249–2255

    CAS  Google Scholar 

  16. El-Khateeb M, Appleton TG, Gahan L, Charles B, Berners-Price SJ, Bolton A (1999) J Inorg Biochem 77:13–21

    PubMed  CAS  Google Scholar 

  17. Barnham KJ, Djuran MI, Murdoch PS, Ranford JD, Sadler PJ (1996) Inorg Chem 35:1065–1072

    PubMed  CAS  Google Scholar 

  18. Bierbach U, Farrell N (1998) J Biol Inorg Chem 3:570–580

    CAS  Google Scholar 

  19. Zhang J, Thomas DS, Davies MS, Berners-Price SJ, Farrell N (2005) J Biol Inorg Chem (Submitted)

  20. Davies MS, Cox J, Berners-Price SJ, Barklage W, Qu Y, Farrell N (2000) Inorg Chem 39:1710–1715

    PubMed  CAS  Google Scholar 

  21. Djuran IM, Lempers ELM, Reedijk J (1991) Inorg Chem 30:2648–2652

    CAS  Google Scholar 

  22. Vrana O, Brabec V (2002) Biochemistry 41:10994–10999

    PubMed  CAS  Google Scholar 

  23. Barnham KJ, Djuran IM, Murdoch P, Ranford JD, Sadler PJ (1995) J Chem Soc Dalton Trans 3721–3726

Download references

Acknowledgement

This research was supported by operating grants from National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Chemistry, Virginia Commonwealth University, Richmond, VA, 23284-2006, USA

    Michael E. Oehlsen, Alexander Hegmans, Yun Qu & Nicholas Farrell

Authors
  1. Michael E. Oehlsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander Hegmans
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yun Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicholas Farrell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicholas Farrell.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00775-005-0036-y.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oehlsen, M.E., Hegmans, A., Qu, Y. et al. Effects of geometric isomerism in dinuclear antitumor platinum complexes on their interactions with N-acetyl-L-methionine. J Biol Inorg Chem 10, 433–442 (2005). https://doi.org/10.1007/s00775-005-0009-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-005-0009-1

Keywords

Search

Navigation